Rats given streptozotocin develop diabetes mellitus and a glomerulopathy characterized by mesangial thickening and deposition of immunoglobulins and complement. When implantation of pancreatic islets into diabetic rats achieves normoglycemia, the mesangial thickening and immune deposits may regress. The objectives of our proposed research are two: (1) to study the pathophysiology of Streptozotocin-induced diabetic nephropathy in rats, focusing both on alterations in overall renal function and on alterations in the determinants of ultrafiltration kinetics and permselectivity properties of glomerular capillaries and (2) to utilize this disase model of diabetic nephropathy for the study of end-organ responsiveness to the treatment of diabetes by islet cell implantation. Diabetes will be induced in the Munich strain of Wistar rats which have glomeruli on the renal cortical surface that are accessible to micropuncture. The servo-null micropipet transducer technique will be utilized for direct measurement of the determinants of effective hydraulic permeability of the diseased glomerulus. In addition, the permselectivity of the glomerular capillary to varying sizes of macromolecules will be determined. The abnormalities in renal function and glomerular permeability will be re-examined after normoglycemia is achieved in these rats by means of islet cell transplantation. These studies will be accomplished using standard micropuncture techniques and clearance methods Studies to date have demonstrated that chronically diabetic rats do not develop impairment of glomerular filtration rate but manifest marked proteinuria which diminishes in response to successful islet transplantation. Permselectivity studies with neutral dextran show that the proteinuria is not associated with alterations in pore size of glomerular capillaries. Marked proteinuria develops as early as one week after induction of diabetes. The mechanism of the proteinuria remains to be elucidated